Ioannis Milioglou1,2, Ioannis Farmakis3, Mandy Neudeker4, Zeeshan Hussain5,4, Avirup Guha5,4, George Giannakoulas3, Vassiliki Kotoula6, Maria Papaioannou7. 1. Case Western Reserve University, Cleveland, OH, USA. ioannismilioglou@gmail.com. 2. University Hospitals Cleveland Medical Center, Harrington Heart and Vascular Institute, Cleveland, OH, USA. ioannismilioglou@gmail.com. 3. Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece. 4. University Hospitals Cleveland Medical Center, Harrington Heart and Vascular Institute, Cleveland, OH, USA. 5. Case Western Reserve University, Cleveland, OH, USA. 6. Hematology Unit, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece. 7. Pathology Department, AHEPA University Hospital, Thessaloniki, Greece.
Abstract
BACKGROUND: Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review. METHODS: We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence. RESULTS: 33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75-0.84), mortality (15%, CI 0.11-0.19) and thromboembolic adverse events (3%, CI 0.02-0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13-0.32). Heterogeneity was significant (Ι2 > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled. CONCLUSION: Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.
BACKGROUND: Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review. METHODS: We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence. RESULTS: 33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75-0.84), mortality (15%, CI 0.11-0.19) and thromboembolic adverse events (3%, CI 0.02-0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13-0.32). Heterogeneity was significant (Ι2 > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled. CONCLUSION: Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.
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